Neutrophils play a key and essential role in the innate immune response against candida infection, which is the most frequent oral manifestation of HIV infection. Results obtained with neutrophils isolated from blood of HIV-infected individuals have variously demonstrated that neutrophils of HIV-infected individuals display increased apoptosis, constitutive activation, and diminished responsiveness to inflammatory stimuli. It is not known, however, how HIV infection influences the functional status of neutrophils within the oral cavity. It is postulated that an alteration in neutrophil function contributes to the increased incidence of candidiasis and periodontal disease in HIV-infected individuals. Moreover, a second role for neutrophils in HIV infection is suggested by the findings that neutrophils bind HIV-1 and increase infection of T lymphocytes as well as increase viral replication in HIV-infected PBMC. Consistent with this postulated role, increased shedding of HIV-1 is observed with gingival linear erythema, which is frequently associated with candida infection and, thus, also an influx of neutrophils into the oral cavity. The relationship between the neutrophil functional status and the capacity of neutrophils to enhance HIV infection and replication, however, is not known. This relationship may be directly relevant to the vertical transmission of HIV infection to infants via breast-feeding by HIV+ mothers, which remains an important route of infant HIV infection in underdeveloped countries. Indeed, oral candidiasis in infants is a risk factor for the vertical transmission of HIV infection via breast milk by HIV+ mothers. Accordingly, this proposal has two specific aims. (1) Does dysregulation of neutrophil function contribute to the increased incidence of oral candidiasis and periodontal disease in HIV-infected patients? (2) Does activation or apoptosis alter the capacity of neutrophils to bind HIV and/or to enhance HIV infection and replication of macrophages or lymphocytes? It is proposed that the results of this study will provide important insight into the essential role of neutrophils in innate immunity within the oral cavity of HIV-infected patients and also into a possible role of neutrophils in the vertical transmission of HIV infection. As such, the results may provide an additional target to enhance innate immunity within the oral cavity and also to decrease the vertical transmission of HIV in breast milk. [unreadable] [unreadable]